Antibodies directed against idiotypic determinants on anti-staphylococcal nuclease antibodies from different mouse strains have been produced in rats and in pigs. The idiotypes are detected by hemagglutination assays and by the inhibition of antibody-mediated inactivation of nuclease. The latter assay is specific for the combining sites (variable regions) of antinuclease antibodies, since extensive absorption of anti-idiotype sera with normal mouse immunoglobulins fails to diminish their activity, and since antibodies to other sites on the Ig molecule do not inhibit inactivation. By screening a variety of strains and offspring from appropriate matings between strains for the presence of idiotypes and other markers, it has been shown that idiotype expression is linked to the heavy chain allotype marker and not to the immune response gene locus. A number of recombinants between different idiotype markers have been found and may provide tools for fine-structure mapping of heavy chain variable region genes. In vivo effects of anti-idiotype antibodies are also being assessed.